Antibodies derived from mom's gut microbes
Research in mice shows antibodies derived from mom's gut microbes protect newborns from E. coli infection
Science Daily/January 8, 2020
Harvard Medical School
Newborn mice derive protective antibodies from their mothers' microbiota. Antibodies derived from mothers' microbiota ward off both localized and widespread systemic infections by the bacterium E. coli. Study points to the role of maternal microbes in offspring protection and neonatal immunity. Findings can inform development of microbe-based therapies against infectious diarrhea in infants.
Mother's milk has been long touted for its salutary effects on the newborn and its ability to shield infants from certain infections.
Now research from Harvard Medical School conducted in mice shows that at least part of its protective effects come from a surprising source: the microbes residing in maternal intestines.
The new study, published Jan. 8 in Nature, shows that antibodies made in response to one particular organism in the maternal gut are passed on to the offspring both via milk and through the placenta to protect newborn pups from infection by at least one disease-causing, and potentially lethal, microbe, E. coli.
The findings add to a growing body of evidence pointing to the potent role of the microbiota -- the trillions of microbes that dwell in the gut, skin, mouth and other parts of the bodies of mammals, including humans -- in disease and health.
But the new research goes a step further -- it specifically identifies maternal microbiota as source of newborn immunity. It further suggests that the intestinal microbiota could offer immune protection even when mothers have had no prior encounters with an infection that allows them to build and pass on protective antibodies to their offspring.
"Our results help explain why newborns are protected from certain disease-causing microbes despite their underdeveloped immune systems and lack of prior encounters with these microbes," said study senior investigator Dennis Kasper, professor of immunology in the Blavatnik Institute at Harvard Medical School. "Moreover, they raise the possibility that mothers can confer immune protection to their offspring even to pathogens that they haven't themselves encountered in the past."
If affirmed through further studies, the findings could inform the design of microbial therapies against dangerous infections such as E. coli and other disease-causing organisms, the researchers said.
"Albeit preliminary, we are hopeful these insights could inform the development of vaccines derived from commensal microbial molecules as a way to prevent infectious diseases," said Kasper, who is also the William Ellery Channing Professor of Medicine at Brigham and Women's Hospital. "Another therapeutic avenue could be the use of commensal microbes as probiotics that protect against diarrheal disease."
Infectious diarrhea -- most commonly due to E. coli or rotavirus -- is the leading cause of malnutrition and the second leading cause of death globally in children under age 5. It causes 1.7 billion infections and claims more than 520,000 lives a year worldwide, according to the World Health Organization.
Without any prior exposure to microbes, a newborn's immune system is a blank slate. For the first three weeks, a newborn's immune protection is derived entirely from maternal antibodies passed onto the fetus during pregnancy via the placenta, during birth via the birth canal, and shortly after birth via breastfeeding.
In the current study, researchers worked with newborn mice genetically engineered to lack B cells -- the antibody-producing factories of the immune system. Some of the newborn mice were subsequently raised by mothers that were also born without antibody-making B cells, and therefore, lacked protective antibodies. The other newborn mice were raised by mothers that had normal immune systems.
Mice exposed to protective antibodies from their mothers were far more resistant to E. coli infection than mice that were not exposed to such antibodies. It was as if the pups repelled the pathogen, the researchers observed. Indeed, their intestines had 33 times fewer E. coli bacteria than newborn mice lacking maternal antibodies. By contrast, mice pups that were not exposed to protective antibodies developed disseminated E. coli disease.
The researchers were also able to pinpoint the specific organism responsible for inducing the formation of the protective antibodies -- a microbe called Pantoea, member of the Enterobacteriaceae bacterial family, which resides in the intestines of mice and other mammals, including humans.
Furthermore, the experiments showed that the antibodies enter both the intestines and bloodstream of newborns via the neonatal Fc receptor, a molecular channel on the placenta that helps ferry protective antibodies from the mother to the growing fetus. Thus far, the receptor has been known to transfer antibodies through the placenta. However, the experiments conducted in the new study show this receptor also absorbs antibodies derived from milk and ferries them from the intestines and into the bloodstream of the newborn mice, ensuring wider, systemic protection beyond the gut. Adult mice, in which this neonatal receptor loses its function with age, did not transfer protective antibodies from their gut to the bloodstream, the experiments showed.
https://www.sciencedaily.com/releases/2020/01/200108131659.htm
Switching to hunter-gatherer lifestyle may increase diversity in children's gut microbes
August 29, 2018
Science Daily/American Society for Microbiology
Immersing city dwellers in the traditional lifestyle and diet of a rainforest village for two weeks increases the diversity of the visiting children's -- but not the adults' -- gut microbiota. In a small pilot study, researchers show that the immersion visit did little to shift the adults' skin, oral, nasal and fecal microbiota.
An international team of researchers has shown that immersing city dwellers in the traditional lifestyle and diet of a rainforest village for two weeks increases the diversity of the visiting children's -- but not the adults' -- gut microbiota. In a small pilot study published this week in mSphere®, an open-access journal of the American Society for Microbiology, the team shows that the immersion visit did little to shift the adults' skin, oral, nasal and fecal microbiota.
"We wanted to look at the question of whether microbiota change during a drastic, radical change of diet and lifestyle," says Maria Gloria Dominguez-Bello, a microbial ecologist at Rutgers University in New Brunswick, New Jersey who led the study with microbiologist Monica Contreras from the Venezuelan Institute of Scientific Research. "In this village, there was no market economy, no bodega, no Coca-Cola -- so this represented a radical shift in diet from a high percentage of processed foods in urban places to zero processed foods and an all-natural diet."
Dominguez-Bello, along with researchers from New York University and two Venezuelan institutes, took advantage of a visit planned by five, city-dwelling adult visitors -- and two of their children -- to live among an indigenous Yekwana village in the Bolivar State of Venezuela for 16 days. The village has a hunter-gatherer-gardener lifestyle and diet.
Typical fare includes cassava (a starchy, high-fiber tuber), corn, various wild fruits, including plantains, pineapples, and berries, fish, and small amounts of game meat and eggs gathered from wild birds. Visitors had two meals a day that consisted of soup with a bit of fish or meat. The rest of their diet consisted of "all-day snacking on cassava with fruit" says Dominguez-Bello. The visitors also bathed in the river without soap and followed the natural circadian rhythms of their hosts.
"The diet contains very little animal protein and it's very, very high in fiber and very low in fat," compared to Western diets, says Dominguez-Bello.
While it is known that people with traditional diets have higher gut microbiota diversity compared to those with urban diets, it was unknown if urban dwellers could shift the diversity of their microbiota higher simply by following a traditional lifestyle and diet. In the gut, a high diversity of microbes is considered a sign of good health.
Traditional people eat diets rich in unprocessed plant material, which are much more chemically complex compared to processed foods. The smorgasbord of chemicals acts as fuel for a higher variety of microbes. Traditional people use less antimicrobial medicines and compounds in daily life, which might also contribute to their increased gut microbe diversity.
During the 16-day visit, the researchers collected samples from the visitors' skin, mouth, nose, and from a fecal swab. Age-matched samples were also collected from villagers. The samples were sequenced and compared.
Surprisingly, none of the adult visitors' microbiota shifted significantly during the visit, while the two children's gut microbiota trended toward a higher number of total microbial species present. Although these results were not statistically significant and in just two subjects, the researchers saw this as interesting nonetheless, given the children's ages of 4 and 7.
Up to now, it was thought that children's gut microbiota become stable and more 'adult-like' by the time they reach 3 years of age. "This indicates that the window for maturing your microbiome may not be 3 years of age, but longer," says Dominguez-Bello. Her team plans to do a larger study with 12 children participating in an "immersion summer camp" to a traditional village.
Because the children's gut microbiota exhibited more plasticity, these results raise an interesting possibility that urban children who eat a more traditional, high-fiber, low-fat and low-processed diet early in life might cultivate a more diverse set of gut microbes. Conversely, adults may have a limited response due to their low microbiome plasticity.
Dominguez-Bello was not terribly surprised that the adults' gut and other microbiota changed so little: "If you take traditional people and bring them to New York, give them antibiotics and McDonald's to eat everyday, it's not surprising that they lose diversity," she says. "But if, as an urban dweller, you've already lost that gut microbe diversity and you move to a high-diversity diet, maybe you cannot 'bloom' diversity because you simply don't have those microbes present anymore."
https://www.sciencedaily.com/releases/2018/08/180829133429.htm
Modeling the microbiome
Physicists develop new mathematical approaches to analyze interactions between gut bacteria
December 5, 2018
Science Daily/University of California - Santa Barbara
The gut microbiome -- the world of microbes that inhabit the human intestinal tract -- has captured the interest of scientists and clinicians for its critical role in health. However, parsing which of those microbes are responsible for effects on our wellbeing remains a mystery.
Taking us one step closer to solving this puzzle, UC Santa Barbara physicists Eric Jones and Jean Carlson have developed a mathematical approach to analyze and model interactions between gut bacteria in fruit flies. This method could lead to a more sophisticated understanding of the complex interactions between human gut microbes.
Their finding appear in the Proceedings of the National Academy of Sciences.
"Especially over the past 20 years or so, scientists have been finding that the microbiome interacts with the rest of your body, with your immune system, with your brain," said Jones, a graduate student researcher in Carlson's lab. "Many diseases are associated with certain microbial compositions in the gut."
The human gut microbiome as yet is too diverse to fully analyze. Instead, the research team, led by Carnegie Institution for Science biologist Will Ludington, used the fruit fly as a model organism to tease apart how the presence of particular gut bacteria could lead to physical and behavioral effects in the host organism.
In their paper, "Microbiome interactions shape host fitness," Carlson, Jones, Ludington and colleagues examine the interactions between five core species of bacteria found in the fly gut, and calculate how the presence or absence of individual species influences aspects of the fly's fitness, including lifespan, fertility and development. "The classic way we think about bacterial species is in a black-and-white context as agents of disease -- either you have it or you don't," Ludington said. "Our work shows that isn't the case for the microbiome. The effects of a particular species depend on the context of which other species are also present."
Building on previous research that found the presence versus the absence of bacteria affected the longevity of an organism (sterile hosts lived longer), the researchers' work on this project revealed that the situation is far more nuanced. For example, the presence of certain bacteria might increase the host's fecundity, while others might decrease longevity. "As we examined the total of what we call a fly's fitness -- it's chances of surviving and creating offspring -- we found that there was a tradeoff between having a short lifespan with lots of offspring, versus having a long lifespan with few offspring," Ludington explained. "This tradeoff was mediated by microbiome interactions."
To decipher these interactions, Ludington performed a combinatorial assay, rearing 32 batches of flies each inhabited by a unique combination of the five bacteria. For each bacterial combination, Ludington measured the fly's development, fecundity and longevity. The analysis of the interactions required Carlson and Jones to develop new mathematical approaches.
"One model that often would be a starting point would be to consider the interactions between pairs of bacteria," said Carlson, whose research delves into the physics of complex systems. "This research shows us that a strictly pairwise model does not capture all of the observed fly traits."
What the study shows, the researchers said, is that the interactions between the bacterial populations are as significant to the host's overall fitness as their presence -- the microbiome's influence cannot be solely attributed to the presence or absence of individual species. "In a sense," said Jones, "the microbiome's influence on the host is more than the sum of its parts."
The newly developed models could be extended to better understand the interactions of the thousands of different species of bacteria in the human microbiome, which could, in turn, shed light on the many connections to microbiome-affiliated diseases including mood disorders, neurological dysfunctions, autoimmune diseases and antibiotic-resistant superbugs.
"In many cases infections are caused by bacteria that we all have in ourselves all the time, and are kept in check by native gut bacteria," Carlson said. It's not so much that the infection is some new, horrible bacteria, she explained, but that the populations of other bacteria have changed, resulting in unrestricted growth for the infectious bacteria.
"It's really about understanding the population dynamics of these systems," she said.
https://www.sciencedaily.com/releases/2018/12/181205152208.htm
Say Hello to a Healthy Gut and Goodbye to Digestive Problems
By Scott Sanders
<info@cancerwell.org>
Some people can eat whatever they want without any issues. Others have negative reactions to certain foods and diets. If you’re one of many people who experience occasional digestive problems, it’s time to learn about how you can use the food you consume to heal you from the inside out.
Digestive ailments hit everyone at some point in their lives, and they can be temporary inconveniences or chronic conditions. Who hasn’t had diarrhea, constipation, bloating, vomiting, or an upset stomach at some point? But there are many who suffer from serious conditions like gallstones, celiac disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and more. According to Everyday Health, 20 percent of Americans are affected by GERD, over 25 million have gallstones, and approximately 10 to 15 percent are affected by irritable bowel syndrome. Disruptive stomach conditions can be caused by what you eat, but they can also be treated by what you eat.
Nutrition
Eating whole, unprocessed foods is the best way to heal the gut. Learn to read nutrition labelsto see what ingredients make up your food. Preservatives and additives make your digestive system work harder and cause other health issues. Some foreign ingredients simply shouldn’t be eaten. Buy your food fresh rather than from packages. The more ingredients in the food, the more you should avoid it.
Food Elimination
Digestive conditions and autoimmune diseases generally call for special diets. To see which foods affect you in negative ways, try an elimination diet that removes specific foods for one month. You can start by cutting out the foods that typically cause issues (such as gluten, dairy, corn, soy, sugar, and alcohol) and reintroduce them slowly to see how they affect you. Another option is to cut out one thing at a time to monitor any differences. If you’re willing to stick with a strict diet, the autoimmune protocoldiet helps reduce intestinal inflammation.
Gut Health
Since your gut processes all of your body’s nutrients, the health of your digestive tract is important to your overall wellbeing. When things are off in your gut, the rest of your body feels off, too. Gut healthcould affect everything from your brain to your skin to your weight-loss efforts.
Your gut contains both good bacteria and bad bacteria. Known as microbiomes, these microorganisms live inside your digestive tract. The friendly bacteriain your gut include Bifidobacterium, Lactobacillus, Saccharomyces Boulardii, Bacillus Coagulans, and Akkermansia microbes. They protect against harmful microbes, promote digestive health, aid in digestion, improve the immune system, produce vitamins, impact the metabolism, and have other positive effects on intestinal health.
Disease
The good bacteria may prevent and treat diseases, such as inflammatory conditions, heart disease, and even cancer. Gut health is linked to cancer in many ways. Digestive issues are often due to cancer and side effects of treatments. Constipation, nausea, stomach cramps, weight loss, and digestion problems can occur as a result of pain medication, chemotherapy, or the cancer itself.
Sometimes, it’s the gut health that helps treat cancer. An immunotherapy called Checkpoint Inhibition can shrink tumors, but studieshave shown that gut health could have something to do with the patient’s response to it. By altering the gut microbiome, patients develop a better response to the immunotherapy. More good bacteria means better immune cells to kill the cancer cells.
Probiotics
Healthy people who don’t have underlying medical problems may want to consider adding probioticsto their daily routine. Probiotics contain the same helpful microorganisms that are present in our bodies. You can ingest probiotics through supplements or in foods such as yogurt, kefir, kimchi, sauerkraut, tempeh, and kombucha (which also has antioxidants).
Exercise
Let’s not discount the importance of exercise for overall health. A healthy diet can heal your body, but never underestimate the role of physical fitness in a holistic approach to healing digestive ailments. Any form of cardiovascular exercise can help move digestive waste through your system. Yogais a great activity to practice, especially when it comes to reducing bloat.
There is no one-size-fits-all approach to intestinal health and treating digestive disorders. Each body is different. It takes trial and error, listening to your body, and seeing a doctor when natural methods don’t provide results. When the solutions finally do come, you’ll get to relish in the joy of eating again.
Household cleaning products may contribute to kids' overweight by altering their gut microbiota
September 17, 2018
Science Daily/Canadian Medical Association Journal
Commonly used household cleaners could be making children overweight by altering their gut microbiota, suggests a new study.
The study analyzed the gut flora of 757 infants from the general population at age 3-4 months and weight at ages 1 and 3 years, looking at exposure to disinfectants, detergents and eco-friendly products used in the home.
Researchers from across Canada looked at data from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort on microbes in infant fecal matter. They used World Health Organization growth charts for body mass index (BMI) scores.
Associations with altered gut flora in babies 3-4 months old were strongest for frequent use of household disinfectants such as multisurface cleaners, which showed lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae. The researchers also observed an increase in Lachnospiraceae bacteria with more frequent cleaning with disinfectants. They did not find the same association with detergents or eco-friendly cleaners. Studies of piglets have found similar changes in the gut microbiome when exposed to aerosol disinfectants.
"We found that infants living in households with disinfectants being used at least weekly were twice as likely to have higher levels of the gut microbes Lachnospiraceae at age 3-4 months; when they were 3 years old, their body mass index was higher than children not exposed to heavy home use of disinfectants as an infant," said Anita Kozyrskyj, a University of Alberta pediatrics professor, and principal investigator on the SyMBIOTA project, an investigation into how alteration of the infant gut microbiome impacts health.
Babies living in households that used eco-friendly cleaners had different microbiota and were less likely to be overweight as toddlers.
"Those infants growing up in households with heavy use of eco cleaners had much lower levels of the gut microbes Enterobacteriaceae. However, we found no evidence that these gut microbiome changes caused the reduced obesity risk," she said.
She suggests that the use of eco-friendly products may be linked to healthier overall maternal lifestyles and eating habits, contributing in turn to the healthier gut microbiomes and weight of their infants.
"Antibacterial cleaning products have the capacity to change the environmental microbiome and alter risk for child overweight," write the authors. "Our study provides novel information regarding the impact of these products on infant gut microbial composition and outcomes of overweight in the same population."
A related commentary provides perspective on the interesting findings.
"There is biologic plausibility to the finding that early-life exposure to disinfectants may increase risk of childhood obesity through the alterations in bacteria within the Lachnospiraceae family," write epidemiologists Dr. Noel Mueller and Moira Differding, Johns Hopkins Bloomberg School of Public Health, in a related commentary.
They call for further studies "to explore the intriguing possibility that use of household disinfectants might contribute to the complex causes of obesity through microbially mediated mechanisms."
Dr. Kozyrskyj agrees and points to the need for studies that classify cleaning products by their actual ingredients. "The inability to do this was a limitation of our study."
The research study was funded by the Canadian Institutes of Health Research (CIHR) with funding from the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence for the CHILD study.
https://www.sciencedaily.com/releases/2018/09/180917082435.htm